Stem cell factor (SCF) is an early-acting hematopoietic cytokine which elicits multiple biological effects. SCF is dimeric and occurs in soluble and membrane-bound forms. It transduces signals by ligand-mediated dimerization of its receptor, Kit. Kit is a receptor tyrosine kinase related to the receptors for platelet-derived growth factor (PDGF) and to those for vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), macrophage colony-stimulating factor (M-CSF) and Flt-3 ligand. The kinase portions of these receptors are closely related and their ligand-binding portions all comprise immunoglobulin-like (Ig) repeats, although these vary widely in sequence and also in a number. Determined here is the crystal structure of selenomethionyl soluble human SCF at 2.2 Å resolution by multiwavelength anomalous diffraction (MAD) phasing. SCF has the characteristic helical cytokine topology, but the structure is unique apart from core portions. The SCF dimer has a symmetric ‘head-to-head’ association. Potential Kit-binding sites on the SCF dimer surface are located. A superposition of this dimer onto VEGF in its complex with the Flt-1 receptor places the binding sites on SCF in positions of topographical and electrostatic complementarity with the Kit counterparts of Flt-1. Similar models can be made for the complex of PDGF with its receptor and FGF-heparin.